The purpose of the proposed project is to assess the role of angiotensin and sodium sensitive structures of the forebrain in experimental hypertension. Ablation of these structures previously has been shown to prevent several forms of experimental hypertension in the rat. The present study will attempt to confirm this finding in the rabbit, and further clarify the mechanism of the effect. Since forebrain mediated responses to increased intra-cerebral concentrations of angiotensin and sodium are primarily concerned with maintenance of body fluid volume and electrolyte concentration, these factors will be studied most intensively. Interactions between body fluid volume and autonomic circulatory control also will be emphasized. The effects of forebrain lesions, and/or chronic pharmacological blockade of periventricular angiotensin receptors in the brain, on three forms of experimental hypertension will be examined in rabbits with regular measurement of alterations in cardiovascular, autonomic and fluid parameters. An attempt also will be made to produce, and characterize, hypertension dependent upon continuous intra-cerebral infusions of angiotensin or sodium chloride. In addition, forebrain modulation of cardiovascular, renal and autonomic responses to acute volume expansion will be studied in conscious rabbits and anesthetized cats. Experiments utilizing electrophysiological analysis of peripheral sympathetic nerve activity, and hypothalamic unit activity, during acute volume expansion in cats will assess possible forebrain modulation of "volume-sensitive" baroreflexes involved in the control of autonomic nerve activity. This project may reveal an important interaction between neural regulation of body fluid homeostasis and neural regulation of the cardiovascular system in hypertension.